Antioxidant Supplementation to Support Dark Adaptation and AMD

By John M. Nolan, PhD

Some of the most commonly prescribed supplements for age-related macular degeneration (AMD) are ones that claim to provide “the AREDS formulation.”[1,2] The AREDS trials have been important in providing a proof of concept that antioxidant supplementation reduces risk of AMD; however, newer research has confirmed the essential role of the specific antioxidants of the macula—the macular carotenoids (lutein, meso-zeaxanthin, and zeaxanthin).[3-5]

Focusing on Deficiencies

When you supplement diet, the main goal is to address deficiency. So, what do we need in our eye supplement? Let’s look at the antioxidants in the AREDS formulation, which include: lutein and zeaxanthin, zinc, vitamins C and E, and copper. We know that the average Western-based diet is extremely deficient in the macular carotenoids. An optimal carotenoid formulation that has been clinically tested is the 10:10:2 mg/day formulation provided by MacuHealth LP.[4,5] Although the additional nutrients found in the AREDS supplement are generally recognized as important and healthy, they are actually not deficient in the average diet. Specifically, 80mg of zinc—the recommended dose in the AREDS formula—is potentially toxic to someone who already consumes a diet containing meat, as most Americans do. Therefore, zinc supplementation must be taken with caution. Additionally, there is sufficient Vitamin C in our diet, but given that it is water-soluble, it won’t harm if consumed in excess.

Carotenoids for Dark Adaptation Speed

It is my view that the benefit of supplementation with the macular carotenoids will be most effective pre-retinal-disease, given the preventative antioxidant actions of these nutrients. Dark adaptation, the process by which our eyes adjust to darkness after being exposed to light, is limited in AMD.[6] Drusen formation limits the transport of vitamin A across the retinal pigment epithelium resulting with compromised rod photopigment during dark adaptation. Stringham et al have demonstrated that the macular carotenoids are significantly associated with dark adaptation speed.[7]

While dark adaptation represents an option to identify patients at early stages of AMD who may benefit from carotenoid supplementation, it is advisable to use a retinal eccentricity that lies outside the extent of the macular carotenoids absorption (e.g., 12 degrees), when performing such assessments.

Note: Acknowledgment for Professor Jim Stringham, Duke Eye Center, for supporting this article.


  1. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8.Arch Ophthalmol2001;119:1417-1436.

  2. Age-Related Eye Disease Study 2 Research G, Chew EY, Clemons TE, et al. Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3.JAMA Ophthalmol2014;132(2):142-149.

  3. Bernstein PS, Li B, Vachali PP, et al. Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease.Prog Retin Eye Res2016;50:34-66.

  4. Akuffo KO, Beatty S, Peto T, et al. The impact of supplemental antioxidants on visual function in nonadvanced age-related macular degeneration: a head-to-head randomized clinical trial.Invest Ophthalmol Vis Sci2017;58(12):5347-5360.

  5. Nolan JM, Power R, Stringham J, et al. Enrichment of macular pigment enhances contrast sensitivity in subjects free of retinal disease: central retinal enrichment supplementation trials - report 1.Invest Ophthalmol Vis Sci2016;57(7):3429-3439.

  6. Owsley C, McGwin G, Jr., Clark ME, et al. Delayed rod-mediated dark adaptation is a functional biomarker for incident early age-related macular degeneration.Ophthalmology2016;123(2):344-351.

  7. Stringham JM, Garcia PV, Smith PA, et al. Macular pigment and visual performance in low-light conditions.Invest Ophthalmol Vis Sci2015;56(4):2459-2468.